Abstract
The newly emerging variants of SARS-CoV-2 from South Africa (B.1.351/501Y.V2) and Brazil (P.1/501Y.V3) have led to a higher infection rate and reinfection of COVID-19 patients. We found that the mutations K417N, E484K, and N501Y within the receptor-binding domains (RBDs) of the virus could confer ~2-fold higher binding affinity to the human receptor, angiotensin converting enzyme 2 (ACE2), compared to the wildtype RBD. The mutated version of RBD also completely abolishes the binding of bamlanivimab, a therapeutic antibody, in vitro . Detailed analysis shows that the ~10-fold gain of binding affinity between ACE2 and Y501-RBD, which also exits in the high contagious variant B.1.1.7/501Y.V1 from the United Kingdom, is compromised by additional introduction of the K417/N/T mutation. Mutation of E484K leads to the loss of bamlanivimab binding to RBD, although this mutation does not affect the binding between RBD and ACE2.
Keywords: ACE2; B.1.1.7/501Y.V1; B.1.351/501Y.V2; COVID-19; P.1/501Y.V3; RBD; Bamlanivimab; SARS-COV-2.
【저자키워드】 COVID-19, ACE2, SARS-CoV-2., bamlanivimab, RBD, B.1.1.7/501Y.V1, B.1.351/501Y.V2, P.1/501Y.V3, 【초록키워드】 Brazil, Mutation, antibody, angiotensin converting enzyme 2, variant, in vitro, virus, angiotensin converting enzyme, bamlanivimab, binding affinity, Reinfection, South Africa, N501Y, K417N, therapeutic, E484K, receptor, infection rate, United Kingdom, COVID-19 patients, binding, Analysis, angiotensin, RBDs, leads, enzyme, wildtype, contagious, receptor-binding domains, variants of SARS-CoV-2, the receptor-binding domain, not affect, mutated, 【제목키워드】 in vitro, 501Y.V2, binding, variants of SARS-CoV-2,